This is diversity measured by hill number indices where increasing hill number (Q) corresponds with more focus on the largest clonotypes. For example, Q=0 is just the number of clonotypes, Q=1 is shannon index, Q=2 is the inverse simpson index, Q=\(\infty\) is 1/(proportion of the largest clone).
This is measuring the diversity of the PBMC TIL matching repertoire
This is the clonality of the TILs themselves (all pretreatment)
This is change over time in the proportion of peripheral blood cells that have TIL matching TCRs
These are just the rarefaction curves from last week:
This is specific for TIL clone sizes and as with the hill numbers, NR are much more clonal
All of these are pretreatment - the first 4 lynch, the next 4 NLR, the last 4 some of the nonresponders
Not sure how we want to represent this since there is a lot of variation among the patients. There are expanded L patients as well as one for NR that’s pretty expanded, kinda variable.
## # A tibble: 15 x 7
## CDR3.aa V.name J.name Clones Proportion expTil cluster_fine
## <chr> <chr> <chr> <int> <dbl> <dbl> <chr>
## 1 CASSVAPSGDGGGTGELFF TRBV9 TRBJ2-2 1042 0.186 34 CD8 TEMRA
## 2 CASSTGAGDTYEQYF TRBV9 TRBJ2-7 503 0.0898 217 CD8 TEMRA
## 3 CASSDYNEQFF TRBV11-2 TRBJ2-1 486 0.0868 47 CD8 TEMRA
## 4 CASSSYNEQFF TRBV11-2 TRBJ2-1 192 0.0343 60 CD8 TEMRA
## 5 CASSPITGTGHYGYTF TRBV6-5 TRBJ1-2 161 0.0288 95 CD8 TEMRA
## 6 CSVRANTEAFF TRBV29-1 TRBJ1-1 154 0.0275 168 CD8 TEMRA
## 7 CASSLVTGTGSYGYTF TRBV6-5 TRBJ1-2 153 0.0273 35 CD8 TEMRA
## 8 CASSERPDYGYTF TRBV2 TRBJ1-2 111 0.0198 61 CD8 TEMRA
## 9 CASSELGTGYDEQFF TRBV2 TRBJ2-1 110 0.0196 46 CD8 TEMRA
## 10 CASSVEAGENTDTQYF TRBV9 TRBJ2-3 103 0.0184 19 CD8 TEMRA
## 11 CASSYAASYEQYF TRBV6-5 TRBJ2-7 92 0.0164 9 CD8 TEMRA
## 12 CASSFGDEQYF TRBV11-3 TRBJ2-7 77 0.0138 113 CD8 TEMRA
## 13 CSVFRGDRYGYTF TRBV20-1 TRBJ1-2 69 0.0123 2 CD8 TEMRA
## 14 CAWSVQVEAFF TRBV30 TRBJ1-1 60 0.0107 21 CD8 TEMRA
## 15 CASSQYNEQFF TRBV11-2 TRBJ2-1 59 0.0105 63 CD8 TEMRA
Sidenote, the super expanded chord for Lynch-like pretreatment (TRBV9.TRBJ2-2) is all one clonotype from 14-1 which is almost 20% of all cells.
The second most expanded chord though is also from 14-1 (TRBV11-2.TRBJ2-1), but it’s mostly three different expanded clonotypes which each differ by only one amino acid (in the same position) and are all expanded in TILs as well.
The raw VJ gene diversity is not super different and is very skewed especially pretreatment.
Small sidenote: all the points in this section that just have timepoint 1 and 5 - timepoint 5 is a combination of all posttreatment timepoints (3 and 5) that I just labelled 5 for code expediency
Kinda noisy and not generally approaching significance, but Lynch is generally intermediate with NLR as more clonal for CD8 and NR more clonal for CD4. Not sure how much we can read from this pattern since this masks a lot of the more granular cell types.
A bit stochastic, but even with the cell count correction, Lynch like has CD8 TEMRA clonality intermediate between NR and the more clonal NLR. Soooo, Lynch clonality is driven by TEMRA being more clonal and Lynch having more TEMRA, not by Lynch-TEMRA specifically being more clonal.
Hard to pick patterns from T cell one - if anything, NLR might be the most distinct with a lower CD8 pre/posttreatment.
From overall, we can much more clearly see the dominance of CD8 in Lynch-like, but it also makes CD4 and other seem somewhat more even.
NR consistently has lower proportion tumor matching at all timepoints and groups. Lynch has higher CD8 especially pretreatment, less different/interpretable for CD4s.
These are all density plot for all cell types pretreatment. Unlike the nebulosa plots, these are calculated for each patient\(x\)timepoint combination and then averaged.
Lynch-like
NLR
Nonresponder
Also worth noting is that I haven’t normalized the color scaling for these, so the highest cell density for nonresponder is about 0.009 while the highest for NLR and lynch are around 0.013, so the graphs are not currently comparable.